Alternatives to amalgam should satisfy the primary requirements of biocompatibility, conservation of tooth structure, adhesion to tooth structure, handling insensitivity, restoration of defective or missing tooth structure, good esthetics, durability, and a high lifetime-to-cost ratio. Because of the known technique sensitivity of alternative restorative materials in use today as demonstrated by the variability in reported clinical performance, the proposed research will focus on the development of a restorative system with an integrated engineered structure that is designed to minimize technique sensitivity. In addition, our research will focus on complementary materials that will enhance adhesion of the bonding agent/restorative material system to dentin, and that will ensure superior clinical performance compared with amalgam. The overall objective of this Center proposal is to develop a complete restorative material system, consisting of a dentin conditioner, dentin-bonding agent, a resin-based composite, resin cement, and a ceramic for inlays and crowns. The proposed system will be designed to 1) release, under demineralizing conditions (pH between 4.0 and 5.5), demineralization indicators, such as 9-aminoacridine, fluoride, remineralizing agents, and bacteria-controlling agents from polymer microspheres, 2) condition dentin effectively via a conditioner/primer consisting of polyacrylic acid modified with amino groups for enhanced compatibility of the bonding agent with demineralized collagen fibers, 3) ensure an effective, hydrolytically stable bond between the bonding agent and enamel, conditioned dentin, cementum, resin-based composites, and ceramics, 4) result in minimal shrinkage during polymerization of novel resin-based composites via selective blending of reactive monomers and sol-gel derived glasses that expand by catalytic hydrolysis, 5) provide water-impermeable coatings on surfaces of glass-ceramic and alumina-based restorations, and 6) restore decayed, damaged, or discolored teeth esthetically and with minimal reduction of tooth structure using glass-ceramic and alumina-based alumina-core ceramic with a reduced thickness of 0.5 to 1.3 mm. Four novel technological approaches will be employed in this material development program: 1) on- demand controlled release from polymer microspheres of remineralization agents at rates controlled by specific pH levels, 2) the optimization of dentin conditioning and bonding agents to enhance the penetration of dentin bonding agents within a collagen network, 3) the use of sol-gel and tribochemical protective surface coatings, toughened ceramics (chain- silica and barium-mica glass-ceramics), and high-modulus resin cements to minimize the risk of premature prosthesis fracture and technique sensitivity, and 4) the control of composite polymerization shrinkage by hydrolysis-controlled matrix swelling . Based on the successful completion of biocompatibility tests, one-year clinical feasibility trials of promising products will be conducted in the fifth year. These studies will be supported in part by the University of Florida. This five-year Center program, consisting of four projects, an Administrative/Statistical core, and a Biological/Clinical Core, will be staffed by a multidisciplinary team whose main objective is to develop durable, technique insensitive restorative materials as alternatives to amalgam.